Phytochemical Constituents and Pharmacological Activities of Plants from the Genus Adiantum : a Review

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Available online at http://www.tjpr.org http://dx.doi.org/10.4314/tjpr.v10i5.18 Review Article

Phytochemical Constituents and Pharmacological Activities of Plants from the Genus Adiantum : A Review

C Pan 1, YG Chen 1*, XY Ma 1, JH Jiang 1, F He 1 and Y Zhang 2 1Department of Chemistry, Yunnan Normal University, Kunming 650500, 2School of Pharmacy, Kunming Medical College, Kunming 650031, China.

Abstract

Adiantum is a genus of ca. 200 species in the family Adiantaceae, distributed extensively across the world from cool temperate zones to hot tropical regions. A lot of Adiantum species have been used in traditional Chinese medicine to cure human and animal diseases including relief of internal heat or fever, enhancement of urination, removal of urinary calculus, and sundry other curative claims. Chemical studies have shown the presence of various classes of compounds, the main ones being triterpenoids, flavonoids, phenyl propanoids, steroids, alicyclic acids, lipids and long-chain compounds. The extract of this genus as well as pure compounds isolated from it have been demonstrated to possess multiple pharmacological activities such as analgesic, antinociceptive, anti-implantation, and antimicrobial activities. In this review, we have addressed the phytochemistry and pharmacological activities of the Adiantum species in order to collate existing information on this plant as well as highlight its multi-activity properties as a medicinal agent.

Keywords: Adiantum species, Adiantaceae, Phytochemical constituents, Pharmacological activities.

Received: 10 February 2011 Revised accepted: 13 September 2011

*Corresponding author: E-mail: [email protected]; +86 871 5941089

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INTRODUCTION neohopene, fernane, isofernene, filicane, pteronane and adiane types. The presence of Adiantum is a genus of ca . 200 species in the a large number of the nor-compounds is also family Adiantaceae, distributed extensively a characteristic feature of this genus. over the world from cool temperate zones to Hopane-type triterpenoids, 1-9, were isolated hot tropical regions. As many as 30 species from various Adiantum species, such as A. and 5 varieties are found in China [1]. Half of capillus-veneri, A. edgeworthii, A. the species have been used in traditional monochlamys, A. caudatum, A. incisum, A. Chinese medicine to cure human and animal cuneatum, A. pedatum, A. tetraphyllum and diseases including relief of internal heat or A. lunulactum (syn. A. philippense ) (Table 1, fever, enhancement of urination, removal of Figure 1) [3,15-26]. Isohopane-type urinary calculus, elimination of stasis to triterpenoid, 10 , was isolated from A. resolve swelling, relief of cough, cure of lunulatum [27], and neohopane-type diarrhea and stoppage of bleeding, as well as triterpenoids, 11 -16 were also isolated from treatment of urinary tract infection, calculus, the genus Adiantum (Table 2, Figure 2). hepatitis, hemorrhage, fractures, snakebite, burns and scald [2]. Other migrated hopane or closely related triterpenoids isolated from the genus According to the literature, Adiantum species Adiantum include norhopane-type are a rich source of triterpenes with various triterpenoids, 17 -29 (Table 3, Figure 3), structural skeletons. Besides, flavonoids, fernane-type triterpenoids, 30 -51 (Table 4, phenyl propanoids and sterols have been Figure 4), an isofernane-type triterpenoid, isolated from the genus Adiantum [3-14]. isofernene ( 52 ) isolated from A. These compounds have been reported to monochlamys and A. pedatum [19,40] , show various bioactivities, such as analgesic, adiane-type triterpenoids, 53 -57 , and filicane- antinociceptive, anti-implantation, and type triterpenoids, 58 -67 (Table 5, Figure 5), antimicrobial activities. In this review, we and a pteronane-type triterpenoid, pteron-14- summarize the current knowledge of the en-7α-ol obtained from A.capillus-veneris phytochemistry of the plants as well as the [16]. Secofilicanes 66 and 67 isolated from A. compounds that have been isolated from the cuneatum are the first two secotriterpenoids genus Adiantum . The biological activities of that have been reported in ferns. Adipedatol this genus have also been addressed. (28 ) and filicenal (61 ) are the first two examples of the natural triterpenoids having PHYTOCHEMISTRY the hemiketal and the conjugated aldehyde groups, respectively [23,28,35,40]. Since the 1960s, 124 compounds, including terpenoids, flavonoids, phenyl propanoids, Other pentacyclics include lupane and steroids, alicyclic acids, lipids and long-chain norlupane triterpenoids lup-20(29)-en-28-ol, compounds have been reportedly isolated 24-norlupan-3-one and adiantulupanone from the genus. Triterpenoids and flavonoids isolated from A. capillus-veneris, A. are the dominant constituents within the tetraphyllum and A. venustum [3,47,48]. genus Adiantum . Oleanane triterpenoids olean-12-en-3-one and olean-18-en-3-one were isolated from A. Terpenoids capillus-veneris [15,25]. Noroleanane triterpenoids adininaonol and Eighty-five triterpenoids were isolated from adiantuoleanone were isolated from A. the genus Adiantum [3-5,15-52]. Most of the venustum and A. incisum respectively triterpenoids are pentacyclic and belong to [21,48]. Ursane triterpenoid urs-20-en-16-ol the hopane and migrated hopane or closely was isolated from A. capillus-veneris [47] , related groups such as isohopane, and gammacerane triterpenoids tetrahyma-

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Table 1: Hopane-type triterpenoids from the genus Adiantum

No. Compound name Source* Ref. 1 Hop-22(29)-ene (= Diploptene) A1~A3 15-19 2 17 β,21 β-Epoxyhopane A4 20 3 Adininaneone A5 21 4 Hydroxyhopane (= Hopanol) A1,A2,A6~A8 3,15-17, 22,23 5 Mollugogenol A A9 24 6 6α-Acetoxy-16 β,22-dihydroxy-3-ketoisohopane A1,A9 24,25 7 17,29-Epoxyhopane A1 16 8 Hopan-28,22-olide A1 16 9 3β-Acetoxy-6α-hydroxy-hop-15,17(21)-diene A9 26 * A1=A. capillus-veneris, A2=A. edgeworthii, A3=A. monochlamys, A4=A. caudatum, A5= A. incisum, A6= A. cuneatum, A7=A. pedatum, A8= A. tetraphyllum, A9= A. lunulatum

O O O

1 2 8

Figure 1: Selected hopane-type triterpenoids from the Genus Adiantum

Table 2: Isohopane and neohopane-type triterpenoids from the Genus Adiantum

No. Compound name Source* Ref. 10 3β-Acetoxy-21 αH-hop-22(29)-ene A9 27 11 Neohop-12-ene (= Neohopene) A1~A3,A6,A7 15-18, 23, 28,29 12 Neohop-18-en-12 α-ol A6 30 13 13-Epineohop-18-en-12 α-ol A6 30 14 Neohop-13(18)-ene A3,A4,A7 18, 20, 23,29 15 Neohop-13(18)-en-19 α-ol A6 30 16 Neohopa-11,13(18)-diene A3,A6,A7 18, 23, 28,29 * A1=A. capillus-veneris, A2=A. edgeworthii, A3=A. monochlamys, A4=A. caudatum, A6= A. cuneatum, A7=A. pedatum, A9= A. lunulatum

AcO R 14 H 10 11 15 OH Fig 2 : Selected isohopane and neohopane-type triterpenoids from the Genus Adiantum

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Table 3: Norhopane-type triterpenoids from the genus Adiantum

No. Compound name Source* Ref. 17 Trisnorhopane A1,A6 16,28 18 Isoglaucanone A1,A6,A7 15, 16, 23,28 (= 17 αH-Trisnorhopan-21-one) 19 Glaucanol A A7 23 20 Glaucanol B acetate A6 28 21 21-Hydroxy-30-norhopan-22-one A1,A3,A6,A7,A10,A11 15, 16, 18, 23, 28,31-33 (= 21-Hydroxyadiantone, Hydroxyadiantone) 22 Isoadiantone A1,A3~A7,A12 15,16,18,20,21, 23,28,33-38 23 Adiantone A1~A7,A9,A10,A13 4,5,15-18, 20, 21,23, 28, 31, 36,37,39-41 24 19 α-Hydroxyadiantone A2,A4 17,20 25 29-Norhopan-22-ol A4 4 26 Isoadiantol B [= (22S)-30- A1,A3,A6,A7,A11 15,18, 22, 23,32 Norisohopan-22-ol, Isoadiantol] 27 22,29 ξ-Epoxy-30-norhopane-13 β-ol A9 39 28 Adipedatol A7 23,40 29 Adipedatol Me ether A7 40 * A1= A. capillus-veneris, A2= A. edgeworthii, A3= A. monochlamys, A4 =A. caudatum, A5= A. incisum, A6= A. cuneatum, A7= A. pedatum, A9= A. lunulatum, A10= A. venustum, A11= A. Emarginatum nol, epihakonanediol, ketohakonanol (= from A. tetraphyllum [3] while hyperin and oxohakonanol) and hakonanediol were trifolin have been isolated from A. isolated from A. monochlamys [18]. monochlamys and A. malesianum Tetrahymanol and ketohakonanol were also respectively [6,9]. Quercetin 3-O-(6"- isolated from A. capillus-veneris , A. pedatum , malonyl)-D-galactoside, rutin, isoquercetin, A. emarginatum , A. cuneatum and A. incisum querciturone, kaempferol 3-glucuronide, [22,23,32,33,49]. astragalin, keampferol 3-sulphate, kaempferol 3,7-diglucoside, nicotiflorin and Besides, tetracyclic triterpenoids have been kaempferol 3-O-rutinoside sulfate were isolated from A. venustum , including isolated from A. capillus-veneris lanostane triterpenoids adiantulanosterol, [7,8,10,12,13]. Querciturone and kaempferol lanost-20(22)-en-3,19-ether and adiantulano- 3-glucuronide were also isolated from A. stene, as well as tirucallane triterpenes cuneatum [7]. Isoquercetin has also isolated adiantutirucallenes A and B [48, 50-52]. from A. monochlamys, A. caudatum, A. tetraphyllum, A. venustum and A. Diterpenoids, 8,13-epoxy-14-labden-19-oic aethiopicum [3-6] while astragalin was acid has been isolated from A. emarginatum isolated from A. monochlamys, A. cuneatum, [32], and linear diterpenoids phytol and A. venustum and A. aethiopicum [5, 6,11]. phyten-3(20)-1,2-diol were isolated from A. tetraphyllum [3] . Only one tetraterpenoid, α- Flavanone prunin was obtained from A. carotene monoepoxide was isolated from A. monochlamys and A. aethiopicum venustum [5] . respectively [6]. Flavandiol, leucopelargonidin was isolated from A. venustum [5]. 2',4',6'- Flavonoids Trihydroxychalcone were isolated from A. sulphureum [14]. Flavone C-glucosides Flavonoids (18 of them) have been isolated vitexin and isovitexin were isolated from A. from the genus Adiantum [3-14]. Quercetin, malesianum [9]. keampferol and their glycosides are the most common flavonols. Quercetin was isolated

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R1 Phenyl propanoids

R2 Phenyl propanoids, 1-p-coumarylglucose 6- sulphate, l-p-coumarylglucose 2-sulphate, l- caffeylglucose 3-sulphate, 1-caffeylgalactose R1 R2 6-sulphate and 1-caffeylglucose were 17 H H 18 =O isolated from A. capillus-veneris [8,53] 19 H OH whereas 1-p-coumarylglucose 6-sulphate 20 OAc H R was also obtained from A. pulverulentum 3 [54]. Coumarins methyl-p-coumarate and R 1 psoralen were isolated from A. thalictroides R 2 var hirsutum [4]. A coumarin dimmer, daphnoretin was isolated from A. capillus- veneris [55]. R1 R2 R3

21 OH COCH3 H 22 H COCH3 H Steroids 23 COCH H H 24 3 H COCH3 OH β-Sitosterol has been isolated from A. CH(Me)OH capillus-veneris, A. caudatum , A. tetraphyllum and A. thalictroides var hirsutum [3,4,36,40,56], daucosterol from A. caudatum [4], and stigmasterol and campesterol from A. capillus-veneris [56]. 25 Alicyclic acids H Alicyclic acids, shikimic acid and quinic acid H were isolated from A. capillus-veneris [57]. HO

Lipids

The betaine lipid diacylglyceryl-O-4’-(N,N,N, - 26 trimethyl)homoserine was isolated from A. OH capillus-veneris [58]. Positional analysis of the fatty acids by lipase treatment showed O that palmitic acid is esterified at position 1, and linoleic, linolenic, and arachidonic acids at position 2 of the glycerol moiety of the lipid. Although the trimethylhomoserine lipid 27 has been found in some algal species, this is the first report that it exists in a vascular plant [58].

O OR Other long-chain compounds

R 16-hentriacontanone and hentriacontane 28 H were isolated from A. caudatum [36]. 29 C Besides, arachidonic acid was found in A. H3 Figure 3: Selected norhopane-type triterpenoids pedatum [59]. The essential oil in the roots of from the genus Adiantum A. flabellulatum contained n-decanoic acid

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Table 4: Fernane-type triterpenoids from the genus Adiantum

No. Compound name Source* Ref. 30 Fern-9(11)-en-28-ol A1,A4,A9 15,16,20,39 31 Fern-9(11)-en-25-oic acid A2,A9,A10 17, 39,42 32 Fern-9(11)-en-25-ol A6 30 33 Fern-9(11)-en-6α-ol A9 39 34 Fern-9(11)-en-3α-ol A1 16 35 Fern-9(11)-en-12 β-ol A1 15 36 Fern-9(11)-en-12-one A1 15,16 37 Fern-9(11)-ene (= Fernene, A1~A4,A6,A7,A9 15-18,20,23,28, 37, Davallene) 39,40, 43 38 19 α-Hydroxyfern-9(11)-ene A4 20 39 23-Hydroxyfernene A5,A7 21,23 40 Fern-7-en-3α-ol A1 16 41 Fern-7-en-25-ol A6 30 42 Fern-7-ene= 7-fernene A1~A4,A6,A7 15-20,23,28,40 43 19 α-Hydroxyfern-7-ene A4 20 44 25-Norfern-7-en-10 β-yl formate A6 28 45 Ferna-7,9(11)-diene A1,A3,A4,A7 15,16, 18,20,23,29 46 19 α-Hydroxyferna-7,9(11)-diene A4 20 47 Fern-8-ene A3,A4,A7 18, 20,23 48 7α,8 α-Epoxyfernan-25-ol A6 22,44 49 7β,25-Epoxyfern-8-ene A6 28 50 7β,25-Epoxyfern-9(11)-en-8α-ol A6 22,43 51 8α-Hydroxyfernan-25,7 β-olide A4 20 A1= A. capillus-veneris, A2= A. edgeworthii, A3= A. monochlamys, A4= A. caudatum, A5= A. incisum, A6= A. cuneatum, A7= A. pedatum :

(11.44%), 6,10,14-trimethyl-2-pentadecanone (11.23 %), and nonanoic acid (6.15 %), whereas the essential oil in the leaves of A. flabellulatum contained n-decanoic acid R1 H H (11.77 %) and nonanoic acid (4.01 %) [60]. The essential oil from the leaves of A. R3 edgeworthii contained n-nonanal as the chief constituent [61]. R R R H 1 2 3 Other constituents 30 R2 CH3 H OH 31 COOH H H A saponin glycoside was isolated from A. 33 CH3 OH H capillus-veneris . Study of the hydrolytic products of the saponin revealed a triterpenoid hydroxyhopanone aglycon and the sugar components: galactose, xylose and H H rhamnose. A. capillus-veneris was also contained protein [62]. The essential oil in the O roots of A. flabellulatum contained diethyl H H phthalate [60]. The essential oil in the leaves 47 49 of A. flabellulatum contained 2-isopropenyl- Figure 4: Selected fernane-type triterpenoids from 4a,8-dimethyl-1,2,3,4,4a,5,6,7-octahydrona- the genus Adiantum

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Table 5: Adiane and filicane-type triterpenoids from the genus Adiantum

No. Compound name Source* Ref. 53 Adian-5-en-3α-ol (=Adiantol) A1,A6 16,35 54 Adian-5-ene (=Adianene) A1 16 55 Adian-5-en-25-ol A6 30 56 Adian-5(10)-en-3α-ol A1 16 57 Adianene ozonide (= Adian-5-ene A3 18,45 ozonide) 58 Filic-3-ene (= 3-Filicene, Filicene) A1~A4,A6,A7,A10 4,5,15-20, 23, 28, 32,40 59 Filicenol A A3 18 60 Filicenol B A3,A9 18,39 61 Filicenal A6,A7 23, 28, 35,40 62 Filicenoic acid A7 23 63 4α-Hydroxyfilican-3-one A1 15 64 3α-Hydroxy-4α-methoxyfilicane A4 20 65 Adiantoxide = A1 15, 16,46 3α,4 α-Epoxyfilicane 66 4,23-Bisnor-3,4-secofilic-5(24)- A6 22,44 en-3-al 67 4,23-Bisnor-3,3-dimethoxy-3,4- A6 22,44 secofilic-5(24)-ene A1= A. capillus-veneris, A2= A. edgeworthii, A3= A. monochlamys, A4= A. caudatum, A6= A. cuneatum, A7= A. pedatum

R3 H H H R1 R2 R3 58 R2 R1 H CH3 CH3 O 59 OH CH CH R O 3 3 R 60 H CH3 CH2OH O 61 H CHO CH3 66 CHO 57 62 67 H COOH CH3 CH(OCH3)2

Figure 5: Selected adiane and filicane-type triterpenoids from the genus Adiantum phthalene (10.63%), [1 R-(1 α,7 β,8a α)]- been demonstrated to possess multiple 1,2,3,5,6,7,8,8a-octahydro-1,8a-dimethyl-7- pharmacological activities including (1-methylethenyl)-naphthalene (9.88%), α- analgesic, antinociceptive, anti-implantation, panasinsen (8.11%), 4-tetradecyne (6.63%), and antimicrobial activities. and β-pinene (5.16%) [60]. The essential oil from the roots of A. edgeworthii contained Analgesic activity 2,6-di-tert-butyl p-cresol as the chief constituent [61]. Hexane fraction from A. cuneatum as well as filicene ( 58 ) and filicenal ( 61 ), given PHARMACOLOGICAL ACTIVITIES intraperitoneally, exhibited potent analgesic activity when evaluated in two models of pain The extract of the Adiantum species as well in mice - writhing test and formalin-induced as pure compounds isolated from them, have pain. 58 presented an ID 50 value of 19.5

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µmol/kg body weight (writhing test), being affected by L-arginine-nitric oxide, serotonin, about 7-fold more active than some reference adrenalin and the opioid systems [64]. drugs, such as acetyl salicylic acid and acetaminophen, with the dose of 73.0-247.0, Anti-implantation activity and 140-250 µmol/kg respectively. It also inhibited both phases (neurogenic and Petroleum ether extracts of A. capillus and inflammatory) of the formalin test at 10 mg/kg isoadiantone ( 22 ) were reported to be active (24 µmol/kg). The results confirm and justify as inhibitors of postcoital implantation in rats the popular use of this plant for the treatment [38]. of sorrowful conditions [35]. Ethanol extract of A. venustum demonstrated good analgesic Antimicrobial activity activity with 100 mg/kg when compared with 50 mg/kg [63]. The methanol extract of A. capillus-veneris, A. peruvianum, A. venustum and A. Anti-inflammatory activity caudatum have been tested for their antimicrobial activity against five Gram The chronic anti-inflammatory activity of the positive, six Gram negative (including ethanol extract of A. venustum has been multiresistant Staphylococcus aureus ) evaluated by carrageen-induced paw edema bacterial and eight fungal strains using method. The results, at the two dose levels standard microdilution assay. Maximum tested in rats, indicate significant anti- activity was exhibited by A. venustum inflammatory activity. Maximum inhibition of followed by A. capillus-veneris , A. inflammation was 71.15 % recorded with 100 peruvianum and A. caudatum . The extract of mg/kg of plant extract. A further decrease in A. capillus-veneris had very low MIC value dose level (50 mg/kg) produced an even (0.48 µg/mL) against Escherichia coli , greater decrease in anti-inflammatory activity whereas A. venustum extract activity against [63]. Aspergillus terreus showed an MIC of 0.97 µg/mL. Total phenolic constituents of A. Antinociceptive activity venustum , A. capillus-veneris , A. peruvianum and A. caudatum were 0.81, 0.83, 0.71 and When evaluated against acetic acid-induced 0.52 % w/w (gallic acid equivalent), abdominal constrictions, filicene ( 58 ) (10, 30 respectively, implying that the observed and 60 mg/kg, i.p.) produced dose-related activity may be related to the content of inhibition of the number of constrictions, phenolics [65]. being several times more potent, with ID 50 of 9.17 mg/kg (6.27 - 13.18 mg/kg), than Pradeep et al reported that aqueous and acetaminophen which had an ID 50 of 18.8 alcohol extracts of A. capillus-veneris and A. mg/kg (15.7 - 22.6 mg/kg), diclofenac (ID 50 incisum were effective against A. 12.1, range 9.40-15.6 mg/kg) and tumefaciens ; aqueous and alcohol extracts of acetylsalicylic acid (ID 50 24.0, range 13.1-43.8 A. capillus-veneris and A. lunulatum against mg/kg); the dose was the same as those E. coli and S. typhi; alcohol extract of A. used for the standard drugs. 58 also incisum against Salmonella arizonae ; produced dose-related inhibition of the pain aqueous and alcohol extracts of A. capillus- caused by capsaicin and glutamate, with veneris and A. incisum , and alcohol extract of mean ID 50 values of 11.7 (range 8.51 - 16.0) A. lunulatum against S. aureus [66] . and < 10 mg/kg, respectively. Its antinociceptive action was significantly The methanol extract of A. trapiziforme reversed by atropine, haloperidol, GABAA inhibited the growth of Bacillus megaterium and GABAB antagonists (bicuculline and and Staphylococcus aureus B-43-5. Older phaclofen, respectively.), but was not plants showed more pronounced activity than

Trop J Pharm Res, October 2011;10(5): 688 Pan et al young ones and fertile fronds had greater cells of Bacillus subtilis [70]. Its’ highest activity than vegetative ones [67]. agglutining activity on chicken’s red blood cell reached 2 10 . In addition, it was specific for not Using disk susceptibility tests, the only some marine algae, as well as bacterial, antibacterial activity of adiantone ( 23 ), yeast and tumor cells but also for two species 22,29 ξ-Epoxy-30-norhopane-13 β-ol ( 27 ), of plant harmful germ and bacteria, fern-9(11)-en-28-ol ( 30 ), fern-9(11)-en-25-oic Helminthosporium turcicum and acid ( 31 ), fern-9(11)-en-6α-ol ( 33 ), fern-9(11)- Pseudomonas solanacoarum [71]. ene ( 37 ), filicenol B ( 60 ) and 6-oxofern-9(11)- ene were assayed against Gram negative Insect-molting hormone activity bacteria Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 25619), Leaf material from 64 New Zealand ferns was Salmonella typhi (ATCC 23564) and Gram examined for insect molting hormone activity positive bacteria Bacillus sphaericus (ATCC by using the housefly larvae for bioassay. 14577), Bacillus subtilis (ATCC 6051), and Activity was found in most species including Staphylococcus aureus (ATCC 9144) [39]. the genera Adiantum [72]. Compounds 23, 31, and 37 were highly active against S. typhi and moderately active Other activities against P. aeruginosa , while compound 27 showed moderate activity against S. typhi . Total flavonoids from A. capiuaris-veneris The other compounds did not show showed high scavenging activity on hydroxyl significant activity against the tested bacterial radicals [73]. El-Tantawy et al determined the strains. Interestingly, Gram negative bacteria, antidiabetic and diuretic effects of the alcohol except E. coli , were highly susceptible to and aqueous extracts of A. capillus-veneris compounds 23 , 31 and 37 and comparable as well as the isolated mucilage [55]. Melos with the positive control, kanamycin[39]. et al evaluated the allelopathic potentials of the crude ethanol extract of A. tetraphyllum Alcohol extracts of the rhizome of A. capillus- and its fractions against Lactuca sativa veneris effectively inhibited the proliferation (lettuce) and Allium cepa (onion) seeds [3]. and metabolism activity of rifampicin-resistant The average time of germination of lettuce pulmonary tuberculosis cells [68]. and onion seeds, when subjected to the crude ethanol extract as well as hexane and Antiviral activity AcOEt fractions of A. tetraphyllum , respectively, at a concentration of 1000 mg/L, Using vesicular stomatitis virus in monkey was significantly ( p < 0,05) longer than that cell cultures as test organism, the extracts of for the control. A. capillus-veneris was found to exhibit antiviral activity [69]. CONCLUSION

Agglutinating activity Chemical studies on Adiantum species have revealed that the typical constituents of this Lectin from the leaves of A. flabellulatum had genus are terpenoids and flavonoids. Among a characteristic of glycoproteins, exihibiting them, some exhibit strong bioactivities, agglutinating activity on rabbit erythrocytes, especially analgesic, antinociceptive, anti- as well as human erythrocytes of A, B, or O implantation, and antimicrobial activities. groups, but had no activity on turtle Further phytochemical and biological studies erythrocytes. It agglutinated cells of should be carried out on this genus in order unicellular alga ( Chlorella pyrenoidosa ), to elucidate their active principles and natural or heat-treated cells of yeast mechanisms of action of the active (Saccharomyces cerbvisiae ) and heat-treated constituents.

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ACKNOWLEDGEMENT 13. Nung VN, Bezanger-Beauquesne L, Torck M. Characterization of flavonoids. Plant Med Phytother, 1971; 5: 177-187. The work was supported by a grant (No. 14. Wollenweber E. Some new external flavonoids from 2005DFA30670) for international collabora- American ferns. Flora, 1979; 168: 138-145. tive research by Ministry of Science and 15. Nakane T, Maeda Y, Ebihara H, Arai Y, Masuda K, Takano A, Ageta H, Shiojima K, Cai SQ, Technology, China and a grant (No. Abdel-Halim OB. Fern constituents: 2009CC018) from Yunnan Province of China Triterpenoids from Adiantum capillus-veneris. for basic research in social development. Chem Pharm Bull, 2002; 50: 1273-1275. 16. Nakane T, Arai Y, Masuda K, Ishizaki Y, Ageta H, Shiojima K. Fern constituents: six new REFERENCES triterpenoid alcohols from Adiantum capillus- veneris. Chem Pharm Bull, 1999; 47: 543-547. 1. Delectis Flora Reipublicae Popularis Sinicae Edita, 17. Shiojima K, Ageta H. Fern constituents: triterpenoids Flora Reipublicae Popularis Sinicae, Tomus isolated from the leaves of Adiantum 3(1), Beijing, China, Science Press, 1990; pp edgeworthii. Structures of 19- 173-214. hydroxyadiantone and fern-9(11)-en-25-oic 2. Wu CY. Outline of New China Herbals, Vol. 3, acid. Chem Pharm Bull, 1994; 42: 45-47. Shanghai, China, Shanghai Press of Science 18. Shiojima K, Arai Y, Kasama T, Ageta H. Fern and Technology, 1990, pp 664-668. constituents: triterpenoids isolated from the 3. Melos JLR, Silva LB, Peres MTLP, Mapeli AM, leaves of Adiantum monochlamys. Filicenol A, Faccenda O, Anjos HH, Torres TG, Tiviroli SC, filicenol B, isoadiantol B, hakonanediol and Batista AL, Almeida FGN, et al. Chemical epihakonanediol. Chem Pharm Bull, 1993; 41: composition and evaluation of allelopathic 262-267. potentials of Adiantum tetraphyllum Humb. & 19. Ageta H, Iwata K, Natori S. Fern constituents. Bonpl. ex. willd (Pteridaceae). Quim Nova, Adianene, filicene, 7-fernene, isofernene, and 2007; 30: 292-297. diploptene. Triterpenoid hydrocarbons isolated 4. Gupta M, Bagchi A, Roy SK, Ray AB, Chemical from Adiantum monochlamys. Tetrahedron constituents of a member of Adiantum Lett, 1964; 5: 3413-3418. caudatum complex. J Indian Chem Soc, 1990; 20. Tsuzuki K, Ohashi A, Arai Y, Masuda K, Takano A, 67: 86-88. Shiojima K, Ageta H, Cai SQ. Triterpenoids 5. Rangaswami S, Iyer RT. Chemical examination of from Adiantum caudatum. Phytochemistry, Adiantum venustum. Curr Sci, 1967; 36: 88- 2001; 58, 363-367. 89. 21. Hayata S, Rahmana A, Choudhary MI, Khan KM, 6. Hasegawa M, Akabori Y. Flavonoid pattern in Latif H, Bayer E. Two new triterpenes from Pteridaceae. I. Flavonoid glycosides obtained fern Adiantum incisum. Z Naturforsch, 2002; from the fronds of Adiantum aethiopicum and 57b: 233-238 . A. monochlamys. Shokubutsugaku Zasshi, 22. Shiojima K, Arai Y, Nakane T, Ageta H, Cai SQ. Fern 1968; 81: 469-472. constituents: Adiantum cuneatum. III. Four 7. Akabori Y, Hasegawa M. Flavonoid pattern in the new triterpenoids, 4,23-bisnor-3,4-secofilic- pteridaceae. II. Flavonoid constituents in the 5(24)-en-3-al, 4,23-bisnor-3,3-dimethoxy-3,4- fronds of Adiantum capillus-veneris and A. secofilic-5(24)-ene,7,25-epoxyfern-9(11)-en-8- cuneatum. Shokubutsugaku Zasshi, 1969; 82: ol and 7,8-epoxyfernan-25-ol. Chem Pharm 294-297. Bull, 1997; 45: 1608-1610. 8. Imperato F. New phenolic glycosides in the fern 23. Shiojima K, Sasaki Y, Ageta H. Fern constituents: Adiantum capullis-veneris L. Chem Ind, 1982; triterpenoids isolated from the leaves of (23): 957-958. Adiantum pedatum. 23-Hydroxyfernene, 9. Murakami T, Wada H, Tanaka N, Kido T, Iida H, Saiki glaucanol A and filicenoic acid. Chem Pharm Y, Chen CM. Chemical and chemotaxonomical Bull, 1993; 41: 268-271. studies of Filices. LXV. A few new flavonoid 24. Brahmachari G, Chatterjee D. Triterpenes from glycosides. (2). Yakugaku Zasshi, 1986; 106: Adiantum lunulatum. Fitoterapia, 2002; 73: 982-988. 363-368. 10. Imperato F. A new acylated flavonol glycoside from 25. Abdel-Halim OB, Ibraheim ZZ, Shiojima K. Oleanane the fern Adiantum capillus-veneris. Chem Ind, triterpenes from Adiantum capillus-veneris 1982; (16): 604.. growing in Egypt. Alex J Pharm Sci, 2002; 16: 11. Akabori Y. Flavonoid pattern in the Pteridaceae IV. 87-92. Seasonal variation of the flavonoids in the 26. Mukherjee KS, Mondal S, Sohel SMA, Mukherjee P, fronds of Adiantum monochlamys. Bot Mag, Chatterjee D, Brahmachari G. A new triterpene 1978; 91: 137-139. from Adiantum lunulatum Burm. Indian J 12. Imperato F. Kaempferol 3-sulfate in the fern Chem, 2003; 42B: 2665-2667. Adiantum capillus-veneris. Phytochemistry, 27. Mukherjee KS, Brahmachari G, Chatterjee D, 1982; 21: 2158-2159. Mukherjee P. Triterpene from Adiantum

Trop J Pharm Res, October 2011;10(5): 690 Pan et al

lunulactum. J Indian Chem Soc, 2001; 78: (Hook et Grev.) de la Sota. Rev Latinoam 267-268. Quim, 1991; 22: 5-6. 28. Shiojima K, Arai Y, Nakane T, Ageta H. Fern 42. Banerjee J, Datta G, Dutta CP, Eguciii T, Fujimoto Y, constituents: Adiantum cuneatum. I. Three Kakinuma K. Fern-9(11)-en-25-oic acid, a new triterpenoids, glaucanol B acetate, 7,25- triterpene from Adiantum venustum. epoxyfern-8-ene and 25-norfern-7-en-10-yl Phytochemistry, 1991, 30: 3478-3480. formate. Chem Pharm Bull, 1997; 45: 636-638. 43. Jankowski CK, Aumelas A, Thuery P, Reyes-Chilpa 29. Ageta H, Shiojima K, Arai Y. Fern constituents: R, Jimenez-Estrada M, Barrios H, Diaz E. X- neohopene, hopene-II, neohopadiene, and ray, 1H/13C 2D and 3D NMR studies of the fernadiene isolated from Adiantum species. structures of davallene and adipedatol, two Chem Commun, 1968; (18): 1105-1107. triterpenes isolated from American Adiantum 30. Shiojima K, Arai Y, Nakane T, Ageta H. Fern capillus-veneris. Pol J Chem, 2004; 78: 389- constituents: Adiantum cuneatum. II. Six new 408. triterpenoids, neohop-18-en-12-ol, 13- 44. Shiojima K, Nakane T, Ageta H, Cai SQ. Fern epineohop-18-en-12-ol, neohop-13(18)-en-19- constituents: two new secofilicane ol, fern-7-en-25-ol, fern-9(11)-en-25-ol, and triterpenoids from Adiantum cuneatum. Chem adian-5-en-25-ol. Chem Pharm Bull, 1997; 45: Pharm Bull, 1996; 44: 630-632. 639-642. 45. Ageta H, Shiojima K, Kamaya R, Masuda K. Fern 31. Zaman A, Prakash A, Berti F, Bottari B, Macchia B, constituent: naturally occurring adian-5-ene Marsili A, Morelli I. New nortriterpenoid ketol ozonide in the leaves of Adiantum from two Adiantum species. Tetrahedron Lett, monochlamys and Oleandra wallichii. 1966; 7: 3943-3947. Tetrahedron Lett, 1978; 19: 899-900. 32. Nguyen HD, Phan VK, Chau VM, Tran TH, Tran TH, 46. Giancarlo B, Francesco B, Marsili A. Structure and Choudhary MI. Terpenoids from Adiantum stereochemistry of a triterpenoid epoxide from emarginatum. Tap Chi Hoa Hoc, 2008; 46: Adiantum capillus-veneris. Tetrahedron, 1969; 229-233. 25: 2939-2947. 33. Ageta H, Iwata K, Arai Y, Tsuda Y, Isobe K, 47. Naseri NG, Ashnagar A, Nia SJ. Isolation and Fukushima S. Fern constituents. structural determination of the major chemical Hydroxyadiantone and oxohakonanol isolated compounds possibly found in the leaves of from Adiantum monochlamys. Tetrahedron maidenhair plant (Adiantum capillus-veneris. Lett, 1966; 7: 5679-5684. L) grown around the city of Dezful, Iran Int J 34. Hussain A, Siddiqui HL, Rashid R, Khan KM, Parvez Chem Sci, 2006; 4: 874-880. M. 1-(5a,5b,8,8,11a,13b- 48. Alam MS, Chopra N, Ali M, Niwa M. Normethyl Hexamethyleicosahydro-1H- pentacyclic and lanostane-type triterpenes cyclopenta[a]chrysen-3-yl)-1-ethanone. Acta from Adiantum venustum. Phytochemistry, Crystallogr, 2008; E64: o723. 2000; 54: 215-220. 35. Bresciani LFV, Priebe JP, Yunes RA, Magro JD, 49. Hussain A, Siddiqui HL, Zia-ur-Rehman M, Elsegood Monache FD, Campos FD, Souza MM, MRJ, Khan KM. 4-Hydroxy- Cechinel-Filho V. Pharmacological and 4,6a,6b,9,9,12a,14b- phytochemical evaluation of Adiantum heptamethylperhydropicen-3-one hemihydrate cuneatum growing in Brazil. Z Naturforsch, isolated from Adiantum incisum. Acta 2003; 58c: 191-194. Crystallogr, 2008; E64: o264. 36. Kshirsagar MK, Mehta AR. Ferns in Gujarat State 50. Neeraj C, Sarwar AM, Mohammad A, Masatake N. A (India) for presence of antibacterial substances new lanostane triterpenic ether from Adiantum of ferns. Planta Med, 1972; 22: 386-390. venustum. Pharmazie, 2000; 55: 538-539. 37. Khosa RL, Wahi AK, Mukherjee AK. Chemical 51. Neeraj C, Sarwar AM, Mohammad A, Masatake N. studies on Adiantum caudatum. Curr Sci, Isolation and characterization of two novel 1978; 47: 624.. triterpenes from Adiantum venustum. Indian J 38. Murthy RSR, Basu DK, Murti VVS. Anti-implantation Chem, 2001; 40B: 350-353. activity of isoadiantone. Indian Drugs, 1984; 52. Neeraj C, Sarwar AM, Mohammad A, Masatake N. A 21: 141-144. novel tirucallane triterpene from Adiantum 39. Reddy VLN, Ravikanth V, Rao TP, Diwan PV, venustum. Pharmazie, 1997; 52: 412-413. Venkateswarlu Y. A new triterpenoid from the 53. Imperato F. Sulfate esters of hydroxycinnamic acid- fern Adiantum lunulatum and evaluation of sugar derivatives from Adiantum capillus- antibacterial activity. Phytochemistry, 2001; veneris. Phytochemistry, 1982; 21: 2717-2718. 56: 173-175. 54. Cooper-Driver GC, Swain T. Sulfate esters of caffeyl- 40. Ageta H, Iwata K. Fern constituents. Adipedatol, and p-coumarylglucose in ferns. filicenal, and other triterpenoids isolated from Phytochemistry, 1976; 14: 2506-2507. Adiantum pedatum. Tetrahedron Lett, 1966; 7: 55. El-Tantawy M, El-Sakhawy F, El-Deeb K, Fathy M, 6069-6074. Hassan AK. A phytochemical and 41. Erazo S, Garcia R, Mendez F, Latorre I, Negrete R. pharmacological study of Adiantum capillus Secondary metabolites of Adiantum veneris L. growing in Egypt. Zagazig J Pharm thalictroides Willd. ex. Schlecht var hirsutum Sci, 1994; 3: 97-103.

Trop J Pharm Res, October 2011;10(5): 691 Pan et al

56. Marino A, Elberti MG, Cataldo A. Phytochemical exert antinociceptive effect in mice. Pharmacol analysis of Adiantum capillus-veneris. Biochem Be, 2009; 93: 40-46. Bollettino, 1989; 65: 461-463. 65. Singh M, Singh N, Khare PB, Rawat AKS. 57. Minamikawa T, Yoshida S. Occurrence of quinic acid Antimicrobial activity of some important in the ferns. Shokubutsugaku Zasshi, 1972; Adiantum species used traditionally in 85: 153-155. indigenous systems of medicine. J 58. Sato N, Furuya M. Isolation and identification of Ethnopharmacol, 2008; 115: 327-329. diacylglyceryl-O-4'-(N,N,N-trimethyl)- 66. Pradeep P, Leena P, Achaleshwar B. In vitro homoserine from the fern Adiantum capillus- antibacterial activity of fronds (leaves) of some veneris L. Plant Cell Physiol, 1983; 24: 1113- important pteridophytes. J Microbiol 1120. Antimicrob, 2010; 2: 19-22. 59. Gellerman JL, Schlenk E. Occurrence of arachidonic 67. Kshirsagar MK, Mehta AR. Ferns in Gujarat State and related acids in plants. Experientia, 1964; (India) for presence of antibacterial substances 20: 426-427. of ferns. Planta Med, 1972; 22: 386-390. 60. Kang WY, Ji ZQ, Wang JM. Composition of the 68. Tan YY, Xiang YM. Effects of the alcohol extracts essential oil of Adiantum flabellulatum. Chem from rhizoma Adiantum capillus-veneris on Nat Compd, 2009; 45: 575-577. rifampicin-resistant pulmonary tuberculosis 61. Ji ZQ, He GD, Kang WY. HS-SPME-GC-MS Analysis cells. J Wuhan Univ Sci Eng, 2003; 16: 79-83. of the essential oil in common Adiantum 69. Husson GP, Vilagines R, Delaveau P. Research into edgeworthii. Zhongguo Yaofang, 2008; 19: the antiviral properties of some natural 2359-2360. extracts. Ann Pharm Fr, 1986; 44: 41-48. 62. Mahran GH, El-Alfy TS, El-Tantawy M, El-Sakhawy 70. Yu P, Zheng Y, Liu YR. Characteristics of F. Chemical constituents of Adiantum capillus glycoproteins in Adiantum flabellulatum lectins. veneris, growing in Egypt. Al-Azhar J Pharm J Trop Subtrop Bot, 2004; 12: 57-62. Sci, 1994; 13: 1-14. 71. Yu P, Liu YR, Zheng Y. Comparison of cell 63. Hussain MM, Muthuprasanna P, Srinivasarao T, agglutination and Bacteriostasis of lectins from Velraj M, Shanmugapandian P, Suriaprabha K. two Pteridophytes. J Fujian Norm Univ, 2004; Analgesic and antiinflammatory activity of 20: 77-81. Adiantum venustum. Res Rev Biosci, 2008; 2: 72. Russell GB, Fenemore PG. Insect molting hormone 102-104. activity in some New Zealand ferns. New Zeal 64. De Souza MM, Pereira MA, Ardenghi JV, Mora TC, J Sci, 1971; 14: 31-35. Bresciani LF, Yunes RA, Delle Monache F, 73. Lin YR, Ding LJ. Extraction and determination on Cechinel-Filho V. Filicene obtained from clearance rate of hydroxyl radicals of flavonoid Adiantum cuneatum interacts with the from Adiantam capillus-veneris. Food Mach; cholinergic, dopaminergic, glutamatergic, 2008; 24: 63-66. GABAergic, and tachykinergic systems to

Trop J Pharm Res, October 2011;10(5): 692